PubMed HealthSearch

Biomedical subjects

M Hjelm

Publications and source records attributed to M Hjelm.

At least 19 recordsLinked to original sources

Study of the relationship between estimates of enzyme kinetic parameters.

Previous indications of an intrinsic relationship between estimates of Km and Vmax calculated from the Michaelis-Menten equation have been explored further. A mathematically linear relationship could be established for the estimates of the two parameters. The relationship--the trend line--holds whether or not the experimental error is linked to the rate of reaction, the substrate concentration or both, provided that the distribution of errors is symmetrical. The practical implication is that enzyme variants with low values of Km and Vmax may not be distinguishable from those with high values of Km and Vmax.

Enzymes

Two methods for assessing the risk-factor composition of the HIV-1 epidemic in heterosexual women: southeast England, 1988-1991.

OBJECTIVE: The prevalence of HIV-1 in the heterosexual population in southeast England between 1988 and 1991 was examined using two methods. DESIGN AND METHODS: First, district neonatal seroprevalence was compared on a geographical basis to social and demographic variables reflecting risk-factor prevalence. Second, over the same period eight children who developed AIDS within the first 12 months of life were born. RESULTS: The differences in seroprevalence between districts could be explained by the proportion of livebirths to women born in parts of Africa. An estimated 92% of neonatal seropositives could be associated with this demographic variable. The proportions of livebirths to women born in other countries, the prevalence of notified injecting drug use, and area measures of social deprivation, were only poorly related to HIV seroprevalence, and had no additional explanatory value. Seven of the eight (87.5%) children who developed AIDS in the first year were born to black women from Africa. CONCLUSIONS: Both methods suggest that a high proportion of heterosexually transmitted HIV in southeast England has been imported.

Adult

Prevalence of maternal HIV-1 infection in Thames regions: results from anonymous unlinked neonatal testing.

To monitor the spread of human immunodeficiency virus (HIV) in the heterosexual population, residues of blood samples collected routinely on absorbent paper for neonatal screening (Guthrie cards) in NE, NW, and SW Thames Regions in England have been tested for antibodies to HIV-1 since June, 1988. 323,369 dried blood spots were analysed to end March, 1991. Prevalence of anti-HIV-1 in newborn babies has remained stable in outer London and non-metropolitan districts whereas prevalence in inner London has increased from 1 in 2000 in the 12 months beginning June, 1988, to 1 in 500 in the first 3 months of 1991. Either exponential or linear growth in the numbers of new seropositives could account for the results. That obstetricians were aware of maternal HIV infection in only 20% of infected pregnancies, indicates the extent to which HIV infection goes unrecognised in the heterosexual community.

Confidentiality

Phenylalanine in whole blood and plasma--a candidate reference method.

A method for the quantification of phenylalanine in whole blood and plasma by isotope dilution gas chromatography-mass spectrometry is presented. The use of an uncommon derivative allows a simple extraction procedure and the most basic mass spectrometer. The relative standard deviation was found to be 1.3% within-batch and 2.1% between-batch under optimum conditions, and the detection limit was found to be 7 pmol injected. The ruggedness of the procedure and sample handling conditions were also examined.

Gas Chromatography-Mass Spectrometry

Prevalence of maternal HIV infection based on unlinked anonymous testing of newborn babies.

This pilot study established that unlinked anonymous testing of dried blood spots routinely collected on Guthrie cards for neonatal screening is a feasible method for monitoring HIV prevalence in women at the time of delivery. The method was sensitive, specific, and less expensive than more conventional ELISAs. 114,515 dried blood spots taken from cards collected in three Thames regions were tested for antibody to HIV-1. 28 samples were confirmed to be antibody positive by western blot (seroprevalence 0.24 per 1000). Unlinked anonymous screening of newborn babies should be extended to monitor the spread of HIV infection in the heterosexual population and to target preventive strategies and provision of health care.

Agglutination Tests

The urea cycle in the Rett syndrome.

The in vivo functioning of the urea cycle in the Rett syndrome (RS) was investigated using alanine load test. The test was carried out in girls with RS and their mothers. These results were compared with those on normal females, males and obligate carriers for ornithine carbamoyltransferase deficiency. Post load hyperammonaemia was not seen in any of the RS girls who were not on medication (valproate). Increased orotate excretion was found in some of the RS girls and mothers. The pattern of urinary excretion of orotate in RS girls and their mothers after a standardised alanine load was similar to that found in female carriers of OCT deficiency. This finding can be explained by a mutant OCT, subject to the Lyon effect, and linked to the gene abnormality in RS or by the presence of an abnormal X-linked mitochondrial protein synthesised in cytoplasma and positioned in close proximity to OCT. Such a protein abnormality could also affect mitochondrial functions in other cells, e.g. in the developing brain.

Adult

Age dependency of the lactase persistence and lactase restriction phenotypes among children in Sri Lanka and Britain.

All neonates are born with intestinal lactase activity. In most of them the intestinal lactase activity is lost during childhood (lactase restriction phenotype). In a minority of children normal intestinal lactase activity is retained (lactase persistence phenotype). In this study the progression of the lactase restriction phenotypes has been studied in 94 Sri Lankan children by oral lactose loads and 162 British children by intestinal lactase estimation (adult Sri Lankans and British predominantly belong to the lactase restriction and lactase persistence phenotypes, respectively). Lactase was present in infancy at birth in all Sri Lankan children and declined around the age of eight years, the majority (59 per cent) of the 10-15-year-olds belonging to the lactase restriction phenotype. In contrast the majority of the British children (95 per cent of all the British children studied) demonstrated the lactase persistence phenotype. The low prevalence rate of the restriction phenotype found among British children was largely contributed by children of African and Asian origin.

Age Factors

Temperature effects on the estimation of free levels of phenytoin carbamazepine and phenobarbitone.

Serum samples from patients on phenytoin (PHT), carbamazepine (CBZ), or phenobarbitone (PB) monotherapy were filtered at 15, 25, and 37 degrees C and the free concentrations measured by high-performance liquid chromatography. The mean apparent dissociation constants at each temperature were calculated, and were used to predict free drug levels from a further series of patients' samples in which total drug and albumin concentrations only were known. The correlation coefficients (r) between these predicted free levels and experimental results obtained by analysis of the same samples for PHT, CBZ, or PB were 0.977, 0.968, and 0.998, respectively, at 25 degrees C; at 37 degrees C, the corresponding values of r were 0.975, 0.961, and 0.997, respectively. We then determined free fractions (alpha) of PHT, CBZ, and PB at 25 and 37 degrees C and used these values to derive theoretical target ranges for free levels for each of the three drugs. We discuss the implication of these results for patient care, with special reference to the need to specify temperature and quote the appropriate target range when analyses of free levels of AEDs are carried out.

Blood Proteins

Haemoglobin A/F ratio in neonates at 7 days correlated with birth weight and estimated gestational age.

Haemoglobin (Hb) A and Hb F has been determined in neonates of Afro-Caribbean and North European origin with gestational ages varying from 32 to 42 weeks. There was no difference in the distribution of Hb A/F ratios between the two groups. Only weak correlations could be established between the Hb A/F ratio and the estimated gestational age or birth weight. This would indicate that there is a considerable interindividual variation in the timing of the switching of haemoglobin synthesis from Hb F to Hb A and erythrocyte production from liver to bone marrow and of oxygen affinity of fetal blood. Thus, intra-uterine adjustments of the oxygen release capacity of haemoglobin would have to rest on biochemical mechanisms during the third trimester.

Birth Weight

Transient hyperphosphatasemia of infancy and early childhood: clinical and biochemical features of 21 cases and literature review.

Clinical and biochemical features of transient hyperphosphatasemia of infancy and early childhood are reviewed in 21 patients we have studied and in a further 93 cases reported in the literature. The diagnosis is suggested by the finding of an increased activity of alkaline phosphatase (EC 3.1.3.1) in plasma, typically more than fivefold the adult upper reference limit, in a child under five years of age, without evidence of liver or bone disease. The condition is confirmed by the presence of a characteristic pattern of alkaline phosphatase isoenzymes and by the normalization of the enzyme's activity in plasma within approximately three months. The etiology of the condition and possible mechanisms of the enzyme increase are discussed.

Age Factors

Packing materials suitable for rapid, analytical, low-pressure chromatography of haemoglobins on midget columns.

Rapid, quantitative, chromatographic separations of mixtures of human haemoglobins have been performed on short (5-20 mm) columns of packing material. The desirable characteristics of suitable column packing materials are illustrated and discussed. Simple, inexpensive, manually operated equipment can be used for the analysis, since the specifically designed midget columns generate little back pressure (10-30 lb/in2) when eluted at constant flow rates up to 2 mL/min. Cation exchange chromatography on bonded silicas has been used for the detection of pathological haemoglobinopathies. Separations similar to the HPLC procedures are possible with the correct selection of buffer composition. It also compares favourably with the methods in common clinical use employing electrophoresis on cellulose acetate. Both ion-exchange and affinity methods for the estimation of glycated haemoglobins have been developed and are compared.

Chromatography, Ion Exchange

Characterization of increased synthesis of acute phase proteins from plasma concentration measurements: a system analysis of the ideal situation with use of computer simulation.

A method for characterizing the secretion of acute phase proteins in vivo from serial plasma concentration measurements is presented. By using a simple two-compartment model it was found that descriptive parameters could be derived from the time course of the increased plasma concentration of the protein. It was assumed that the secretion of an acute phase protein is adequately described by: (i) the start time t1; (ii) the end time t2; (iii) the magnitude of increased flux of the protein from synthetic sites to the extracellular space, described by a turnover index, S. The influence of sampling interval and analytical precision on the reliability of the estimated parameter values was investigated in the ideal situation by using computer simulation. It was found that informative estimates of the secretion rate of an acute phase protein could be obtained provided a fairly high analytical precision with a coefficient of variation less than or equal to 0.01 and using a sampling interval between 0.5--2 h.

Adrenocorticotropic Hormone

Drug interference in clinical chemistry: studies on ascorbic acid.

The expert group "Drug Interference in Clinical Chemistry" of the Bureau of Reference, Directorate General for Research, Science and Education of the Commission of the European Communities, consisting of one participant of each member of the European Communities, presents this first report on the final results of its activities. Within the framework of a first stage basic program, the paper describes interferences of therapeutic and elevated doses of ascorbic acid on commonly used clinical chemical methods. This is the result of a bipartite study that was jointly planned, carried out and evaluated. Local and personal influences have been eliminated, as have variations due to methodology, measurement equipment and reagents, in order to be able to present distinct causal effects of ascorbic acid. No definite influence of ascorbic acid on analytical values for urea, cholesterol, calcium, protein, bilirubin, aspartate aminotransferase and alkaline phosphatase could be detected. At therapeutic concentrations, ascorbic acid distinctly interferes with the analysis of glucose, uric acid, creatinine and inorganic phosphate. The extent and direction of interferences vary, depending on the type of reaction, kit and apparatus. In some cases the influence of ascorbic acid results in severe disturbance of the analytical methods leading to useless values.

Ascorbic Acid